Phase Behavior, Functions, and Medical Applications of Soy Phosphatidylcholine and Diglyceride Lipid Compositions

Abstract

Lipid compositions with the ability to self-assemble into biocompatible nano-and mesostructured functional materials have many potential uses in modern medicine. By using twocomponent lipid systems, it is possible to tune the structure formation and related functional properties, e.g., the encapsulation and extended release of small molecules and peptides, by simply varying the ratio of the lipid building blocks. This is shown in detail for the binary phosphatidylcholine and diglyceride lipid systems, which are currently being used in multiple programs for the development of novel pharmaceuticals and marketed products.The ability of certain lipids to self-assemble into functional reversed-phase nonlamellar liquid crystal (LC) gels in contact with aqueous media, make such systems highly interesting for use as ambient responsive delivery systems using such functional features as bioadhesion, biodegradation, encapsulation, and controlled release.1 By exploiting the liquid-to-LC gel transition triggered on exposure of lipid solutions to aqueous media, it is possible to combine excellent in vivo encapsulation and extended release properties of some reversed LC gel phases, with the easy manufacturing and administration properties of relatively low-viscosity nonaqueous lipid solutions comprising small amounts of nonaqueous solvent. 1,2The most frequently used nonlamellar LC-forming lipid in drug delivery-related studies has been glycerol monooleate (GMO).3,4 At physiological conditions in excess water, GMO forms a bilayer-based bicontinuous cubic phase (V 2 ) with the Pn3m space group representing a three-dimensional network of hydrophilic and hydrophobic domains. Although a promising candidate for several applications, GMO-based LCs have been shown to exhibit a pronounced tendency to disrupt membrane structures, e.g., extensive hemolytic activity.5 Furthermore, the one-component GMO system has further limitations with respect to the drug delivery application in the difficulty of compensating for any phase changes caused by solubilizing drug compounds. 6 The use of a two or multicomponent system can typically alleviate this issue and can allow for compensation of unwanted phase changes by simply adjusting the ratio of the lipid building blocks. One example of such a system is the two-component unsaturated (e.g., dioleoyl) phosphatidylcholine (PC) and glycerol dioleate (GDO) system, where PC has a preference for the planar lamellar LC phase (L ¡ ) and GDO for the reversed liquid micellar phase (L 2 ). Between these extremes at full hydration reversed 2D hexagonal (H 2 ), reversed micellar cubic (I 2 ) with the Fd3m space group as well as two-and three-phase regions are formed. 711A recent study on the in vitro release of disodium fluorescein from soy PC (SPC)/GDO nonlamellar LCs has shown that the minimum of release (lowest release rates) can be found for compositions in the two-phase region between the H 2 and I 2 phases.1 Importantly, the observed release of both for small molecules 1 and peptides 2 from these phases ...

Advances in the delivery of buprenorphine for opioid dependence

“…A depot buprenorphine preparation that uses a different delivery strategy from poly lactide-coglycolide microcapsules is based on the characteristics of certain low-viscosity lipids in contact with aqueous media to self-assemble into reversed-phase “water-in-oil” nonlamellar liquid crystal nanoparticle gels. 77 , 78 The preparation CAM2038 uses this technology (FluidCrystal ® ; Camurus AB, Lund, Sweden) to deliver buprenorphine in a low-viscosity two-lipid medium that can be delivered through a small 23-gauge needle as a premixed weekly or monthly subcutaneous injection. After injection, the depot, in contact with interstitial aqueous fluid, transforms into a viscous liquid-crystal gel phase that elutes buprenorphine at a predictable rate as the depot is biodegraded.…”

Influence of the hydrophobic domain on the self-assembly and hydrogen bonding of hydroxy-amphiphiles

“…27,28 Moreover, more recently DOG has been increasingly used as an essential component of formulations for encapsulation of drugs or effectors. 29,30 As far as we are aware, there is only one IR-spectroscopic work devoted to diacylglycerol, but rather in complexes with phosphatidylethanolamine than as a pure compound. 31 The present study is aimed to explore how ODA and DOG assemble in supramolecular phases and what is the role of H-bonds and the hydrophobic domain in this process.…”

Fate of Liposomes in the Presence of Phospholipase C and D: From Atomic to Supramolecular Lipid Arrangement

“… 9 Compositions containing higher DOG mole ratios (generally >50%) mixed with Soy-PC give rise to complex mixtures of phases including 2D hexagonal and reversed micellar cubic, and are of interest as nonlamellar lipid nanoparticle drug delivery vectors. 19 In mixtures of 1,2-dipalmitoyl- sn -glycerol (DPG), POPC, and cholesterol, it has been shown that the DPG acts in a similar manner to cholesterol, i.e., it increases chain order and bilayer thickness, reduces volume per lipid and lateral diffusion of lipids, and induces a strong condensing effect in PC bilayers. 20 A recent single-concentration study of the diacylglycerols DPG, POG, and DOG in POPC membrane bilayers reported that this decrease in lateral diffusion of lipids is proportional to the level of DAG unsaturation.…”